Amygdala-Targeted Transcranial Temporal Interference Stimulation for Major Depressive Disorder: A Randomized Sham-Controlled Trial of Clinical Efficacy and Neurobiological Mechanisms

NCT07829575 | Not Yet Recruiting DMC

• 1 other identifier: PDJW_2026_MDD
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This randomized, sham-controlled clinical trial aims to evaluate the efficacy and safety of amygdala-targeted transcranial temporal interference stimulation (tTIS) in adults with major depressive disorder (MDD) and to explore its potential neurobiological mechanisms. The main questions this study aims to answer are: Whether active amygdala-targeted tTIS reduces depressive symptoms compared with sham stimulation. Whether tTIS produces changes in amygdala-related neural activity and functional brain networks that are associated with clinical improvement. Participants will be randomly assigned to receive either active tTIS or sham stimulation. They will complete a course of stimulation sessions and undergo clinical assessments before and after the intervention. Neuroimaging assessments will also be performed to investigate treatment-related changes in the amygdala and associated brain networks.

Conditions

Major Depressive Disorder (MDD

Keywords

Transcranial Temporal Interference Stimulation; Major Depressive Disorde; Amygdala; Neuromodulation; Neuroimaging

Outcome Measures

Primary Outcomes (1)

• Change in 17-item Hamilton Depression Rating Scale (HAMD-17) Total Score

  The 17-item Hamilton Depression Rating Scale (HAMD-17) is a clinician-rated scale used to assess the severity of depressive symptoms. Total scores range from 0 to 52, with higher scores indicating greater depressive symptom severity. The primary outcome is the change in HAMD-17 total score from baseline to the end of the 10-session intervention.

  Baseline; after 10 stimulation sessions (30 minutes per session; end of Week 2)

Secondary Outcomes (11)

• Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score

  Baseline,after 5 stimulation sessions (30 minutes per session; end of Week 1); after 10 stimulation sessions (30 minutes per session; end of Week 2); and at 1 week and 4 weeks after completion of the 10-session intervention.

• Change in 17-item Hamilton Depression Rating Scale (HAMD-17) Total Score Across Treatment and Follow-up

  Baseline,after 5 stimulation sessions (30 minutes per session; end of Week 1); after 10 stimulation sessions (30 minutes per session; end of Week 2); and at 1 week and 4 weeks after completion of the 10-session intervention.

• Change in Hamilton Anxiety Rating Scale (HAMA) Total Score

  Baseline,after 5 stimulation sessions (30 minutes per session; end of Week 1); after 10 stimulation sessions (30 minutes per session; end of Week 2); and at 1 week and 4 weeks after completion of the 10-session intervention.

• Change in Snaith-Hamilton Pleasure Scale (SHAPS) Score

  Baseline,after 5 stimulation sessions (30 minutes per session; end of Week 1); after 10 stimulation sessions (30 minutes per session; end of Week 2); and at 4 weeks after completion of the 10-session intervention.

• Change in Pittsburgh Sleep Quality Index (PSQI) Global Score

  Baseline,after 5 stimulation sessions (30 minutes per session; end of Week 1); after 10 stimulation sessions (30 minutes per session; end of Week 2); and at 1 week and 4 weeks after completion of the 10-session intervention.

Other Outcomes (3)

• DTI

  Baseline,after 10 stimulation sessions (30 minutes per session; end of Week 2); and at 4 weeks after completion of the 10-session intervention.

• fMRI

  Baseline,after 10 stimulation sessions (30 minutes per session; end of Week 2); and at 4 weeks after completion of the 10-session intervention.

• Incidence of Treatment-Emergent Adverse Events

  From the first stimulation session through the 4-week follow-up

Study Arms (2)

Active tTIS

EXPERIMENTAL

Device: Transcranial Temporal Interference Stimulation

Sham tTIS

SHAM COMPARATOR

Device: Sham Transcranial Temporal Interference Stimulation

Interventions

Transcranial Temporal Interference Stimulation DEVICE

Active transcranial temporal interference stimulation (tTIS) will be delivered using two pairs of scalp electrodes. Two high-frequency alternating currents with slightly different carrier frequencies will be applied to generate a low-frequency temporal interference envelope within the targeted amygdala region. Electrode placement and stimulation parameters will be determined according to the study protocol and individualized electric-field modeling when applicable. Participants assigned to the active group will receive 10 stimulation sessions, with each session lasting 30 minutes, according to the predefined treatment schedule.

Active tTIS

Sham Transcranial Temporal Interference Stimulation DEVICE

Participants assigned to the sham group will undergo the same electrode placement and treatment procedures as the active stimulation group. Sham stimulation will include brief ramp-up and ramp-down periods to mimic the initial sensory experience of active stimulation, without delivering continuous therapeutic stimulation during the remainder of the session.

Sham tTIS

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Aged 18 to 55 years, inclusive, with no restriction on sex.
• Diagnosed with Major Depressive Disorder (MDD) according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), as determined by a study physician.
• A 17-item Hamilton Depression Rating Scale (HAMD-17) score ≥17 at screening/baseline.
• The antidepressant medication regimen must remain stable from at least 30 days before signing the informed consent form through the study period.
• In the judgment of the investigator, the participant or their legally authorized representative is able to understand the purpose and procedures of the study, comply with the study protocol, and provide written informed consent.

You may not qualify if:

• A history of other psychiatric disorders, neurological disorders, or substance abuse that, in the investigator's judgment, may interfere with the assessment of treatment efficacy.
• A history of epilepsy, seizures, or convulsive episodes.
• Presence of intracranial metallic foreign bodies or metallic implants in or near the heart.
• Presence of organic brain disease, or a history of severe head injury or cranial surgery.
• Receipt of electroconvulsive therapy (ECT) or other physical treatments, such as transcranial magnetic stimulation (TMS), within the 30 days before enrollment.
• An unstable psychiatric condition or significant suicide risk, as assessed by the investigator.
• Women who are pregnant or breastfeeding.
• Current participation in another interventional clinical trial.
• Any other condition that, in the investigator's judgment, makes the participant unsuitable for participation in this study.

Sponsors & Collaborators

• Shanghai Pudong New Area Mental Health Center, School of Medicine, Tongji University: lead

Study Sites (1)

Shanghai Pudong New Area Mental Health Center

Shanghai, Shanghai Municipality, 201204, China

Location

MeSH Terms

Conditions

Depressive Disorder, Major

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Central Study Contacts

Jingjing Huang

CONTACT

021-68306699*1222; huangjingjing18@tongji.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: September 3, 2026
• First Posted: September 21, 2026
• Study Start (Estimated): October 20, 2026
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): December 30, 2027
• Last Updated: September 21, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)